Effects of Propofol on Cyclic Strain-induced Endothelin-1 Expression in Human Umbilical Vein Endothelial Cells
Bibliographic record
Abstract
BACKGROUND: Propofol is one of the most popular intravenous induction agents of general anesthesia. Experimental results revealed that propofol exerted hypotensive and antioxidative effects. However, the intracellular mechanism of propofol remains to be delineated. The aims of this study were to test the hypothesis that propofol may alter strain-induced endothelin-1 (ET-1) secretion and nitric oxide production, and to identify the putative underlying signaling pathways in human umbilical vein endothelial cells. METHODS: Cultured human umbilical vein endothelial cells were exposed to cyclic strain in the presence of propofol, and ET-1 expression was examined by Northern blotting and enzyme-linked immunosorbent assay kit. Activation of extracellular signal-regulated protein kinase, endothelial nitric oxide synthase, and protein kinase B were assessed by Western blot analysis. RESULTS: The authors show that propofol inhibits strain-induced ET-1 expression, strain-increased reactive oxygen species formation, and extracellular signal-regulated protein kinase phosphorylation. On the contrary, nitric oxide production, endothelial nitric oxide synthase activity, and protein kinase B phosphorylation were enhanced by propofol treatment. Furthermore, in the presence of PTIO, a nitric oxide scavenger, and KT5823, a specific inhibitor of cyclic guanosine monophosphate-dependent protein kinase, the inhibitory effect of propofol on strain-induced extracellular signal-regulated protein kinase phosphorylation and ET-1 release was reversed. CONCLUSIONS: The authors demonstrate for the first time that propofol inhibits strain-induced ET-1 secretion and enhances strain-increased nitric oxide production in human umbilical vein endothelial cells. Thus, this study delivers important new insight into the molecular pathways that may contribute to the proposed hypotensive effects of propofol in the cardiovascular system.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".